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Antifungal Agent Amphotericin B CAS 1397-89-3 / Yolk Lecithin Powder CAS 93685-90-6 / 97281-48-6

Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis.The fungal infections it is used to treat include aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis. For certain infections it is given with flucytosine. It is typically given by injection into a vein.

Common side effects include a reaction with fever, chills, and headaches soon after the medication is given, as well as kidney problems. Allergic symptoms including anaphylaxismay occur. Other serious side effects include low blood potassium and inflammation of the heart.It appears to be relatively safe in pregnancy. There is a lipid formulation that has a lower risk of side effects.It is in the polyene class of medications and works in part by interfering with the cell membrane of the fungus.

Amphotericin B was isolated from Streptomyces nodosus in 1955 and came into medical use in 1958. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. It is available as a generic medication.The cost in the developing world of a course of treatment as of 2010 is between US$ 162 and 229.

Medical uses

Antifungal

One of the main uses of amphotericin B is treating a wide range of systemic fungal infections. Due to its extensive side effects, it is often reserved for severe infections in critically ill, or immunocompromised patients. It is considered first line therapy for invasive mucormycosisinfections, cryptococcal meningitis, and certain aspergillus and candidal infections.It has been a highly effective drug for over fifty years in large part because it has a low incidence of drug resistance in the pathogens it treats. This is because amphotericin B resistance requires sacrifices on the part of the pathogen that make it susceptible to the host environment, and too weak to cause infection.

Side effects

Amphotericin B is well known for its severe and potentially lethal side effects. Very often, it causes a serious reaction soon after infusion (within 1 to 3 hours), consisting of high fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea and tachypnea, drowsiness, and generalized weakness. The violent chills and fevers have caused the drug to be nicknamed "shake and bake".This reaction sometimes subsides with later applications of the drug, and may in part be due to histamine liberation. An increase in prostaglandinsynthesis may also play a role. This nearly universal febrile response necessitates a critical (and diagnostically difficult) professional determination as to whether the onset of high fever is a novel symptom of a fast-progressing disease, or merely the effect of the drug. To decrease the likelihood and severity of the symptoms, initial doses should be low, and increased slowly. Paracetamol, pethidine, diphenhydramine,  have all been used to treat or prevent the syndrome, but the prophylactic use of these drugs is often limited by the patient's condition.

Intravenously administered amphotericin B in therapeutic doses has also been associated with multiple organ damage. Kidney damage is a frequently reported side effect, and can be severe and/or irreversible. Less kidney toxicity has been reported with liposomal formulations (such as AmBisome) and it has become preferred in patients with preexisting renal injury. The integrity of the liposome is disrupted when it binds to the fungal cell wall, but is not affected by the mammalian cell membrane,^[38] so the association with liposomes decreases the exposure of the kidneys to amphotericin B, which explains its less nephrotoxic effects.^[39]

In addition, electrolyte imbalances such as hypokalemia and hypomagnesemia are also common.^[40] In the liver, increased liver enzymes and hepatotoxicity (up to and including fulminant liver failure) are common. In the circulatory system, several forms of anemia and other blood dyscrasias (leukopenia, thrombopenia), serious cardiac arrhythmias (including ventricular fibrillation), and even frank cardiac failure have been reported. Skin reactions, including serious forms, are also possible.

Amphotericin B is a polyene antifungal agent against a wide variety of fungal pathogens. It binds irreversibly to ergosterol, resulting in disruption of membrane integrity and ultimately cell death.